{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:44:18Z","timestamp":1789015458078,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Autoimmune hepatitis (AIH) is a chronic liver disease that regularly relapses when immunosuppression is tapered. It is thought to be driven by T\u2010cells, whereas the etiologic impact of an apparently deregulated B lineage system, as evidenced by hypergammaglobulinemia and autoantibodies, remains elusive. We set out to investigate T and B cell repertoires supporting chronic inflammation in AIH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>T and B cell receptor (TCR\/BCR) and human leukocyte antigen (HLA) next\u2010generation immunosequencing were used to record immune signatures from a cohort of 60 patients with AIH and disease controls. Blood and liver B lineage immune metrics were not indicative of a dominant directional antigen selection apart from a slight skewing of <jats:italic toggle=\"yes\">IGHV<\/jats:italic>\n                                 <jats:italic toggle=\"yes\">\u2010J<\/jats:italic> genes. More importantly, we found strong AIH\u2010specific <jats:italic toggle=\"yes\">TRBV\u2010J<\/jats:italic> skewing not attributable to the <jats:italic toggle=\"yes\">HLA\u2010DRB1<\/jats:italic> specificities of the cohort. This <jats:italic toggle=\"yes\">TCR<\/jats:italic> repertoire bias was generated as a result of peripheral T cell (de)selection and persisted in disease remission. Using a clustering algorithm according to antigenic specificity, we identified liver <jats:italic toggle=\"yes\">TCR<\/jats:italic> clusters that were shared between patients with AIH but were absent or deselected in patients with other liver pathologies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Patients with AIH show profound and persisting T\u2010cell architectural changes that may explain high relapse rates after tapering immunosuppression. Liver T\u2010cell clusters shared between patients may mediate liver damage and warrant further study.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31473","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T08:41:42Z","timestamp":1595320902000},"page":"1436-1448","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":48,"title":["Next\u2010Generation Immunosequencing Reveals Pathological T\u2010Cell Architecture in Autoimmune Hepatitis"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9789-5776","authenticated-orcid":false,"given":"Christoph","family":"Schulthei\u00df","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV, Oncology\/Hematology,Martin\u2010Luther\u2010University Halle\u2010Wittenberg,Halle 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Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Fanchi","sequence":"additional","affiliation":[{"name":"ENPICOM B.V.,\u2032s\u2010Hertogenbosch,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Bonzanni","sequence":"additional","affiliation":[{"name":"ENPICOM B.V.,\u2032s\u2010Hertogenbosch,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils H.","family":"Wildner","sequence":"additional","affiliation":[{"name":"First Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Schulze Zur Wiesch","sequence":"additional","affiliation":[{"name":"First Department of Medicine,University Medical Center 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